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Biology of reproduction2016; 95(5); 107; doi: 10.1095/biolreprod.116.142687

Rosiglitazone Improves Stallion Sperm Motility, ATP Content, and Mitochondrial Function.

Abstract: Media used for equine sperm storage often contain relatively high concentrations of glucose, even though stallion spermatozoa preferentially utilize oxidative phosphorylation (OXPHOS) over glycolysis to generate ATP and support motility. Rosiglitazone is an antidiabetic compound that enhances metabolic flexibility and glucose utilization in various cell types, but its effects on sperm metabolism are unknown. This study investigated the effects of rosiglitazone on stallion sperm function in vitro, along with the possible role of AMP-activated protein kinase (AMPK) in mediating these effects. Spermatozoa were incubated with or without rosiglitazone, GW9662 (an antagonist of peroxisome proliferator-activating receptor-gamma), and compound C (CC; an AMPK inhibitor). Sperm motility, viability, reactive oxygen species production, mitochondrial membrane potential (mMP), ATP content, and glucose uptake capacity were measured. Samples incubated with rosiglitazone displayed significantly higher motility, percentage of cells with normal mMP, ATP content, and glucose uptake capacity, while sperm viability was unaffected. The percentage of spermatozoa positive for mitochondrial ROS was also significantly lower in rosiglitazone-treated samples. AMPK localized to the sperm midpiece, and its phosphorylation, was increased in rosiglitazone-treated spermatozoa. CC decreased sperm AMPK phosphorylation and reduced sperm motility, and successfully inhibited the effects of rosiglitazone. Inclusion of rosiglitazone in a room temperature sperm storage medium maintained sperm motility above 60% for 6 days, attaining significantly higher motility than sperm stored in control media. The ability of rosiglitazone to substantially alleviate the time-dependent deterioration of stallion spermatozoa by diverting metabolism away from OXPHOS and toward glycolysis has novel implications for the long-term, functional preservation of these cells.
© 2016 by the Society for the Study of Reproduction, Inc.
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Publication Date: 2016-09-28 PubMed ID: 27683266DOI: 10.1095/biolreprod.116.142687Google Scholar: Lookup
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Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

The research article explores how rosiglitazone, an antidiabetic drug, can enhance the motility and function of stallion sperm in vitro, potentially improving long-term preservation. The drug’s effect may be mediated by AMP-activated protein kinase, a cellular energy regulator.

Research Goal and Methodology

  • The researchers aimed to understand the impact of rosiglitazone on the function of stallion sperm, given that the current process of sperm storage media contains high glucose concentrations while stallion spermatozoa primarily utilizes oxidative phosphorylation (OXPHOS) not glycolysis to generate ATP (the source of energy in cells) and support its functionality.
  • They conducted in vitro studies where they exposed the stallion spermatozoa to various conditions including different chemical substances such as rosiglitazone, GW9662 (an antagonist of peroxisome proliferator-activating receptor-gamma), and compound C (an AMPK inhibitor).

Observations and Findings

  • The sperm samples incubated with rosiglitazone showed a significant increase in motility, ATP content, and glucose uptake capacity. Additionally, a higher percentage of cells showed normal mitochondrial membrane potential (mMP).
  • The viability of the spermatozoa remained unaffected despite the rosiglitazone treatment. Further, the presence of mitochondrial ROS (Reactive Oxygen Species) was significantly lower compared to the untreated samples.
  • Upon evaluation, it was found that AMPK, a potential mediator in delivering the effects of rosiglitazone, was present in the midpiece of the spermatozoa. Also, the phosphorylation of AMPK was found to increase in rosiglitazone-treated spermatozoa, suggestive of enhanced energy regulation.

Role of AMPK

  • Compound C, an AMPK inhibitor, was found to reduce the sperm motility and AMPK phosphorylation, further demonstrating the essential role of AMPK in the functionality and energy regulation of spermatozoa.
  • This evidence also indicates that the effects of rosiglitazone on enhancing sperm functionality are potentially facilitated by the action of AMPK.

Long-term Effects

  • The study found that rosiglitazone maintained sperm motility above 60% for up to 6 days in room temperature storage, surpassing the motility of the sperm stored in control media.
  • The researchers concluded that rosiglitazone helps divert the metabolic activity of spermatozoa away from oxidative phosphorylation (OXPHOS) towards glycolysis, thus pacifying time-dependent deterioration and ensued implications for the long-term functional preservation of stallion spermatozoa.

Cite This Article

APA
Swegen A, Lambourne SR, Aitken RJ, Gibb Z. (2016). Rosiglitazone Improves Stallion Sperm Motility, ATP Content, and Mitochondrial Function. Biol Reprod, 95(5), 107. https://doi.org/10.1095/biolreprod.116.142687

Publication

Biology of reproduction
ISSN: 1529-7268
NlmUniqueID: 0207224
Country: United States
Language: English
Volume: 95
Issue: 5
Pages: 107

Researcher Affiliations

Swegen, Aleona
  • Priority Research Centre in Reproductive Science, School of Environmental and Life Sciences, University of Newcastle, Callaghan, New South Wales, Australia aleona.swegen@uon.edu.au.
Lambourne, Sarah Renay
  • Priority Research Centre in Reproductive Science, School of Environmental and Life Sciences, University of Newcastle, Callaghan, New South Wales, Australia.
Aitken, R John
  • Priority Research Centre in Reproductive Science, School of Environmental and Life Sciences, University of Newcastle, Callaghan, New South Wales, Australia.
Gibb, Zamira
  • Priority Research Centre in Reproductive Science, School of Environmental and Life Sciences, University of Newcastle, Callaghan, New South Wales, Australia.

MeSH Terms

  • AMP-Activated Protein Kinases / metabolism
  • Adenosine Triphosphate / metabolism
  • Animals
  • Glycolysis / drug effects
  • Horses
  • Hypoglycemic Agents / pharmacology
  • Male
  • Membrane Potential, Mitochondrial / drug effects
  • Mitochondria / drug effects
  • Mitochondria / metabolism
  • Phosphorylation / drug effects
  • Reactive Oxygen Species / metabolism
  • Rosiglitazone
  • Semen Analysis / veterinary
  • Sperm Motility / drug effects
  • Spermatozoa / drug effects
  • Spermatozoa / metabolism
  • Thiazolidinediones / pharmacology

Citations

This article has been cited 17 times.
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